We are investigating the mechanisms for the assembly of virus particles. these studies are concerned with the genetic control of macromolecular assembly, and exploit knowledge of the genes, proteins, and assembly pathways of bacterial viruses. How are closed shells built? Having found that a recycling scaffolding protein is needed for Phage P22 capsid assembly, we want to determine the actual interaction sequence of the coat, scaffolding, and minor proteins in forming the precursor double shell. During DNA packaging with all dsDNA phages, precursor shells re-organize into mature shells. What are the mechanisms? In P22 the scaffolding protein exists from within the coat protein shell, which itself expands. Analysis of mutant and wild type proheads in an in vitro rearrangement reaction may identify steps in these shell transformations. The attachment of bacteriophage to their host cells in injection of the chromosome requires complex tail structures. We are studying the assembly of the tail organelles of phages P22, lambda, and T4. Two particular focus of study are the maturation of the tail spike protein of P22, and the mechanism for determining the length of the tails of T48 lambda. The ability to assemble a large number of proteins into a functional phage organelle in vitro provides a means of screening chemical agents for their effects on protein-protein and protein-nucleic acid interactions. As an outgrowth of our virus studies, we hope to develop in vitro phage assembly for studying toxicology at the macromolecular level. Our present studies focus on the actions of acridines in inhibiting DNA packaging and DNA injection in phage P22.